Gene Regulation: the ability of cells to control their level of gene expression. (Brooker, G-15)
Francois Jacob and Jacques Monod made the remarkable discovery that "genes" can be ‘regulated’ - that is they can be switched on and off like a water faucet. (Kandel, 256) The process of turning genes on and off. During early development, cells begin to take on specific functions. Gene regulation ensures that the appropriate genes are "expressed" at the proper times. Gene regulation is accomplished by a variety of mechanisms including chemically modifying genes and using "regulatory proteins" to turn genes on or off. (NHGRI) Includes making chemical modifications in "chromatin," organizing DNA structure, and regulating "transcription." (Norman Lectures, 7/22/09) A sizable portion of the “genomes” of complex “organisms” is devoted to gene regulation. Can have a dramatic impact on the ability of organisms to respond to "environmental" changes, "differentiate" cells, and progress through developmental stages. (Brooker, 255-257)
Alternative Splicing: mechanism of combining "exons" of a gene in different ways. (Lewis, 185) Form of gene regulation that allows an organism to use the same gene to make different "proteins" at different stages of development, in different “cell types,” and/or in response to a change in environmental conditions. (Brooker, 272) A process whereby multiple “mRNA” are generated from a single gene. A particular exon may be connected to any one of several alternative exons to form a mature mRNA. The alternative forms of mature mRNA produce "protein isoforms" in which one part of the isoforms is common while the other parts are different. (MeSH) Also referred to as 'alternative RNA splicing.'
Chromatin Remodeling: (process of) adding or removing certain organic chemical groups to or from “histones.” The three major types of small molecules that "bind" to histones are "acetyl groups," "methyl groups," and “phosphate groups.” (This) pattern of binding controls whether the DNA wrapped around the histones is "transcribed" or not. (Lewis, 203) The mechanisms effecting establishment, maintenance, and modification of that specific physical "conformation" of chromatin determining the transcriptional accessibility or inaccessibility of the DNA. (MeSH) One limitation to altering chromatin remodeling to treat inherited disease is that this action could affect the expression of many genes - not just the one implicated in the disease. (Lewis, 204) Editor's note - “Rett syndrome” is a disorder associated with chromatin remodeling. Also referred to as 'chromatin assembly and disassembly.'
Acetylation: the “covalent” (binding) of an acetyl group into an organic molecule. (NCIt) A chemical reaction in which a small molecule called an acetyl group is added to other molecules. Acetylation of proteins may affect how they act in the body. (NCI1) Causes “histones” to loosen grip on DNA, allowing “transcription factors” access to the DNA strand. (Norman Lectures, 7/22/09) Also referred to as ‘histone acetylation.”
Acetyl Groups: a small molecule made of two "carbon" (and) three "hydrogen" (atoms), and one "oxygen" atom. Acetyl groups are added to or removed from other molecules and may affect how the molecules act in the body. (NCI1) Binding can shift histone interactions in a way that eases transcription. The enzyme 'acetylase' adds acetyl groups to the histones. Addition and removal of acetyl groups, methyl groups, or phosphate groups are examples of "epigenetic changes." Enzymes called 'deacetylases' remove acetyl groups which shuts off gene expression. (Lewis, 203)
Methylation: addition of methyl groups. (MeSH) The covalent chemical or biochemical addition of a methyl group to a compound. (NCIt) A chemical reaction in which a small molecule called a methyl group is added to other molecules. Methylation of proteins or nucleic acids may affect how they act in the body. (NCI1) Method that silences gene expression. (Brooker, 272) Inactivates DNA. Acts in genomic “imprinting” by inactivating either paternal or maternal “alleles.” Deficiency may cause “embryonic developmental” abnormalities. (Norman Lectures, 7/22/09) Also referred to as ‘DNA methylation.’
Methyl Groups: a small molecule (CH3) made of one carbon and three hydrogen atoms. (NCI1) When a methyl group binds to a specific amino acid in a histone, a protein is attracted that shuts the DNA off. As methyl groups are added, methylation spreads from the tail of one histone to the adjacent histone, propagating the gene silencing. Methyl groups also control gene expression by binding to "cytosines" in the genome. The 'methlylome' is the collection of all the methylated sites in the genome. (Lewis, 203)
Regulatory Genes: genes whose function is to regulate the expression of other genes. (Brooker, G-31) Specifically, genes which code for proteins which regulate transcription. (MeSH) Those that encode proteins (are) called gene regulatory proteins. (They) switch the "effector genes" on or off. Once the gene has been expressed, the (previously separated) two strands of DNA zip up again, and the gene is shut off until the next time regulatory proteins initiate transcription. There are two types of regulatory genes – “activators” and “repressors.” (Kandel, 257-258) Also referred to as ‘activator genes.’
Effector Genes: those that encode “effector proteins” such as “enzymes” and “ion channels,” which mediate specific cellular functions. Every effector gene has in its DNA not only a “coding region” that encodes a particular protein but also a “control region,” a specific site now known as a “promoter.” Regulatory proteins bind to the promoter of effector sites and thereby determine whether the effector genes are going to be switched on or off. (Kandel, 257)
Enhancers: play a role in the ability of “RNA polymerase” to begin transcription and thereby enhance the rate of transcription. (Brooker, 268)
Response Elements: DNA sequences that regulate the expression of genes. (Brooker, G-32) “Nucleotide” sequences which are recognized by specific regulatory "transcription factors," thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. (MeSH)
Regulatory Proteins: proteins encoded by a regulatory gene which switches an effector gene on or off. (They) bind to the promoter or effector sites and thereby determine whether the effector genes are going to be switched on or off. Help to separate the two strands of DNA and make transcription possible. (Kandel 257, 258) Act as regulators in “anabolic” and “catabolic” reactions. (Norman Labs, 81)
Effector Protein: a protein encoded by an effector gene. (Kandel, 257)
RB1 Protein: the protein 'RB1' normally binds another protein called 'E2F' and keeps it from directing production of the proteins that orchestrate DNA synthesis as cells prepare to divide. A defect in RB1 can cause it to let go of E2F prematurely. Consequently, DNA synthesis occurs before the cell is ready. The cell may divide over and over, released from the normal controls on cell division. Such unregulated cells can grow out of control to cause "cancer." (Batiza, 19)
Transcription Factors: a diverse group of proteins that bind to DNA at specific promoter or enhancer regions. They also bind to DNA-associated proteins to initiate, stimulate, inhibit or terminate transcription. (NCIt) Bind to specific sequences of DNA. (Mikulecky, 249) Aid in the activation and regulation of transcription. ‘Zinc finger proteins’ are one type of transcription factor. (GeneReviews) Direct control of transcription depends on them. Structure includes a DNA-binding domain (area on the protein) that binds to DNA, and a protein-binding domain that recognizes other proteins. (Norman, 7/22/09) (They) influence the ability of RNA polymerase to transcribe genes. (Brooker, 238) Transcription factors can either decrease or increase the rate of transcription of a gene. (Brooker, 258) More abundant before birth because of the extensive cell differentiation of this period. (Lewis, 202)
Activator Protein: agent that promotes the production and release of proteins. (MeSH) Transcription factor that binds to DNA and increases the rate of transcription. (Brooker, G1) An important role of some activators is to diminish the level of chromatin compaction where a gene is located. (Brooker, 270) Also referred to as ‘inducible enzymes,’ ‘inducers,’ ‘activator proteins,’ and ‘activating proteins.’
Repressor Protein: a transcription factor that binds to DNA and inhibits transcription. (Brooker, G-32) A protein that turns off the expression of one or more genes. The repressor protein works by binding to the gene's promoter region, preventing the production of "mRNA." (NHGRI) Repressor genes encode the regulatory proteins that shut genes off. Some genes are repressed for most of the lifetime of the organism. Others are switched on or off in order to achieve optimal function of the cell. (Kandel, 257-258) Also referred to as ‘repressible enzymes’ or ‘repressor proteins.’